The primary objective of this research proposal is to determine the mechanisms of action of histocompatibility linked immune response (Ir) genes. For the Ir-1 gene, all mice develop a T cell independent IgM primary response to large molecular weight lots of the synthetic polypeptide (T,G)-A--L. Responders develop T cell dependent IgG secondary responses whereas non-responders are suppressed and unreactive to subsequent antigen challenge. Studies are designed to test the hypothesis that Ir-1 determines T cell recognition of carrier; and that carrier activated T cells induce switch over from IgM to IgG in hapten stimulated B cells:l. Pre-treatment of responder mice with hapten inhibits the switchover to IgG. Syngeneic cell transfers will be used to determine if the inhibition is effected by hapten induced depletion of reactive B cells. 2. Non-responder mice can be made unreactive to subsequent antigen challenge by pre-treatment with antigen given simultaneously with passively administered antibody. Transfers of syngeneic T or B cells will be utilized to evaluate the role of each of those lymphoid sub-populations in this unreactive state. 3. The effect of lipopolysaccharide on the kinetics of the response to (T,G)-A--L will also be studied.